An inflammatory response is an important element of a host's natural defense mechanism against pathogens and is also involved in wound healing. Despite the beneficial role that the inflammatory response plays in host survival, excessive inflammation may have clinically adverse results in some medical conditions. Sepsis is a disorder arising from infection that results in an excessive inflammatory response.
Intra-abdominal sepsis is often caused by leakage of microorganisms, in particular a specific type of bacteria, from the intestine into the peritoneal cavity. This leakage typically results from complications associated with abdominal surgery, such as the perforation of the large bowel and abdomen, complications subsequent to abdominal surgery, or bowel disease. Numerous clinical and experimental studies have shown that the release of the colonic contents into the peritoneal cavity can lead to wide-spread septicemia.
Traditional approaches for preventing sepsis have involved the use of antibiotics and antimicrobial agents with activity against both the facultative and obligate anaerobic components of the intestinal flora, and particularly against Gram-negative bacteria such as E. coli. However, even with the use of antibiotics, that have had some impact on the infection rate associated with intra-abdominal sepsis, the infection rate is still about 15% for all abdominal surgeries, and 30% for high-risk gastrointestinal surgeries. Since there are in excess of 1.5 million abdominal surgeries performed in the United States every year, and perhaps another 1.5 million surgeries world-wide, the risk of sepsis represents a significant medical problem.
It will be appreciated that there is a need for a pharmaceutical preparation which is capable of protecting a host organism against sepsis and other inflammatory disorders.